Hypoxia results from long-term anti-angiogenic therapy and can stimulate hypoxia-inducible factors (HIFs). HIF-induced hy-poxia signaling is involved in various steps in tumor invasive-metastatic cascade. On the one hand, HIFs regulate epithelial-mesenchy-mal transition. On the other hand, the characteristics of pericytes around vessels and the links among endothelial cells can change;thus, tumor cells can more easily intravasate into blood vessels, survive in peripheral blood, and then reach specific organs, ultimately resulting in metastasis. This review discusses the emerging mechanisms of long-term anti-angiogenic therapy and the occurrence of metastasis.

Objective To investigate the feasibility of the gene therapy on angiogenesis after myocardial infarction in rats.Methods Thirty-six male SD rats,after the ligation of left anterior descending coronary artery,were divided into 2 groups as experimental and control one.Expressions of VEGF were measured by RT-PCR and Immunohistochemistry(IHC).Angiogenesis and capillary density were evaluated by HE stain,and qualitative and quantitative analysis were carried out.The adverse effects were tested after injection of pVEGF165-PLGA nanoparticle.Results Compared with control groups,ischemic myocardial cells persistently and stably expressed VEGF in experimental group;Vascular endothelial cells actively proliferated,and the effect of angiogenesis was significant;48 hours later,nanoparticles were observed in myocardial cells.Conclusion Injection of with pVEGF165-PLGA nanoparticle,it can stimulate effective host-derived angiogenesis,which results in the prevention of impaired cardiac muscle after myocardial infarction.It may be an effect way to treat MI.

Dedifferentiated chondrosarcoma(DDCS)comprises approximately 10%of all chondrosarcomas and has the worst outcome with a 5-year survival of 10%.The preferred localizations are the femur,humerus and pelvis.DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malignancy grade.The diagnosis of DDCS is highly complicated,requiring detailed radiological and histopathological evaluation as well as precise bioptic technique.The dedifferentiated component is typically a high-grade sarcoma(usually grade 3 or 4),which can be either an osteosarcoma,a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma.In approximately one-third of the radiographs,one-third of the MR images,and one-half of the CT scans, the tumors demonskates bimorphic features.Recently,array-based comparative genomic hybridization(array-CGH)studies have been performed on frozen chondrosarcoma(including DDCS)specimens.There is a statistically significant association between high-grade tumor(grade Ⅲ and dedifferent ated)and the recurrent genetic deletions at 5q14.2～q21.3,6q16～q25.3,9p24.2～q12,and 9p21.3.One of the most commonly deleted regions of DDCS involved chromosome 9.Earlier investigations of DDCS showed p53 mutation and p53-LOH in the anaplastic component.It is also accompanied by Rt-LOH.P161NK4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS.While p161NK4,FHIT,and E-cadherin were methylated in highly malignant osteosarcomatous compartment of the tumor.Surgical resection of the tumor within wide or radical margins is the most important treatment.The value of neoadjuvant or adjuvant therapy remain uncertain.Several new drug targets have been identified and phase Ⅱ studies are currently ongoing.Current phase Ⅱ trials open for DDCS patients used the following medicine:apomab(proapoptotic selective agonist of Ap02L/TRAIL death receptor),perifosine(serine/threonine kinase Akt inhibitor),dasatinib(multitargeted small-molecule tyrosine kinase inhibitor),and the combination of gemcitabine and docetaxel.More recently,several phase Ⅰ studies have reported incidental responses of DDCS to newer targeted agents,such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide.The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases.Therefore,early diagnosis and prompt surgical treatment may improve the outcome.

Objective To discuss the effect of polysaccharides from Tegillarca granosa as an adjuvant on pcDNA3.1?Sj26GST vaccine against Schistosoma japonicum infection. Methods Sixty SPF BALB/c mice were divided into four groups randomly(15 mice each group),including a control group,a polysaccharides group,a vaccine group,and a vaccine plus poly?saccharides group. In the 0,2th and 4th week of the experiment,the mice in the above four groups were immunized for 3 times with 100μl PBS,100μg polysaccharides from Tegillarca granosa,100μg Sj26GST vaccine,and 100μg Sj26GST vaccine plus equivalent polysaccharides,respectively. Two weeks after the last immunization,all the mice were infected with 40 ± 1 Schistosoma japonicum cercariae through the skin of the abdomen. After the infection for 6 weeks,all the mice were sacrificed, and their serums,livers and the adult worm of Schistosoma japonicum in them were collected,the specific sera IgG antibodies were detected by ELISA,and the worm reduction rates and egg reduction rates in the liver were calculated. Results Six weeks after the infection,the IgG antibody levels of the mice in the vaccine group and the vaccine plus polysaccharides group were 18.26 ± 0.42 mg/ml and 20.21 ± 0.89 mg/ml respectively,the difference between them were statistically significant,and both of the IgG levels of the above groups were significantly higher than those in the control(both P<0.05). The worm reduction rate and egg reduction rate in the vaccine group were 28.60%and 35.84%,respectively,and the rates in the vaccine plus polysac?charides group were 38.04% and 49.74%,respectively,the differences between the worm reduction rates and egg reduction rates were both statistically significant(both P<0.05). Meanwhile,the two rates in the two above groups were all significantly higher than those in the control group(all P<0.01). Conclusion Polysaccharides from Tegillarca granosa using as an adju?vant can increase the protection effect of pcDNA3.1?Sj26GST vaccine against Schistosoma japonicum infection.

Primary immunodeficiency disease (PID) are rare diseases caused by inherent defects of the immune system,the main clinical manifestations are increased susceptibility to infections,autoimmune diseases and malignancies.For such rare diseases,it's essential to establish national patient online database for collaborative studies.By using hypertext preprocessor (PHP) and MySQL,the database and registration system are successfully set up,and itcould complete inquiries for the information saving,export,query,retrieval,backup etc.This database includes patient's information on the diagnosis,clinical manifestations,laboratory examinations,treatments.Through communication and information-sharing between multiple centers,it creates a basis for nationwide research on PID.

Objective To investigate incidence,risk factors and the prevention strategy of local recurrence 6 months after surgery for metastatic bone tumors.Methods Data of 797 patients who had undergone operations for metastatic bone tumors from March 1997 to March 2012 were retrospectively analyzed.Sixty-three patients (7.9％) who had local recurrence 6 months after operation were enrolled in the recurrence group,including 40 males and 23 females,and the average age at the time of operation was 55.21 years.Seven hundred thirty-four patients were enrolled in the non-recurrence group,including 432 males and 302 females,with an average age of 56.49 years.The risk factors for local recurrence 6 months after operation for metastatic bone tumors were statistically analyzed.Results The statistical analysis showed the risk factors for local tumor recurrence 6 months after surgery for metastatic bone tumors included preoperative general condition (10.9％ vs 6.2％),the rate of progress of the primary tumor (10.1％ vs 6.1％),site of bone metastasis (9.1％ vs 3.9％),surgical method (11.4％ vs 6.4％),whether local radiotherapy was performed preoperatively (28.0％ vs 6.6％),whether local radiotherapy was performed postoperatively (8.7％ vs 2.8％),whether sensitive systemic therapy was performed preoperatively (12.2％ vs 6.1％),whether sensitive systemic therapy was performed postoperatively (10.3％ vs 5.6％) and whether local therapy was performed in primary tumor site (10.1％ vs 5.8％).Multivariate analysis showed the independent risk factors included preoperative general condition (OR=0.534),rate of progress of the primary tumor (OR=2.164),site of bone metastasis (OR=2.906),whether local radiotherapy was performed preoperatively (OR=3.184),whether sensitive systemic therapy was performed preoperatively (OR=2.344) and whether sensitive systemic therapy was performed postoperatively (OR =0.468).Conclusion When the patients has following conditions:poor preoperative general condition,fast progressive primary tumor,metastatic tumor in the axial skeleton,application of local radiotherapy preoperatively,and application of sensitive systemic therapy,the surgical treatment should be chosen cautiously.

Objective:To clarify the effects of the BMP receptor inhibitor LDN-193189 in the dedifferentiated chondrosarcoma (DDCS) cell line NDCS-1 and to explore the anti-tumor mechanism of LDN-193189 in DDCS. Methods:NDCS-1 was treated with 5 nmol/L of LDN-193189. MTT assay and clone formation experiments were used to verify that LDN-193189 suppressed cel proliferation. Transwel and wound healing tests were performed to demonstrate that LDN-193189 inhibited cell invasion. Western blot detection was used to show that LDN-193189 inhibited the suppression of BMPR2, p-Smad1/5, and RUNX2 protein expression. Results:The BMPR2 signaling pathway was inhibited by LDN-193189;thus, cell viability and invasion were significantly suppressed. Conclusion:LDN-193189 induces the inhibition of progression in vitro via the BMPR2-p-Smad1/5-RUNX2 signaling pathway in the human DDCS cell line NDCS-1.

The development and progression of tumors are closely related to the tumor microenvironment.As one of the most important com-ponents in tumor microenvironment,cancer-associated fibroblasts (CAFs)play an important role in carcinogenesis,angiogenesis,inva-sion,and metastasis of tumors.The role of CAFs in the development and progression of hepatocellular carcinoma (HCC)is reviewed by dis-cussing how CAFs are recruited and activated in the tumor microenvironment and how CAFs promote tumor angiogenesis and regulate tumor immunity.This review may provide new approaches for the treatment of HCC.

Objective To anatomically reconstruct massive bone deficiency w it h prosthesis-devitalized bone composites after bone tumor resection. Methods Fr om July 1997 to December 2000, twenty-four patients with malignant bone tumor we re treated with a limb salvage procedure including wide tissue resection and rec onstruction. The resected bone were debrided of gross tumor tissues, and treated with 200 g/L saline for 30 minutes and 95% alcohol for 20 minutes, then the dev italized bone was implanted back to resection sites. Eleven diaphysis defects we re reconstructed with devitalized bone fixed with interlocked intramedullary nai ling, the other 13 defects were reconstructed with prosthesis-devitalized bone c omposites. Results The mean follow-up period was two and half years. One patient s had nonunion at the graft-host junction. There were only two patients(9%) dev eloping local recurrence in half to two years after the surgery. These indicate that this method can be accepted by the limb salvage protocol. Conclusion Prosth esis devitalized bone composite enabled surgeons to reconstruct massive bone def iciency after bone tumor resection. Compared with allografts, devitalized bone h as the following advantages: 1) This technique reduces the rate of nonunion; 2) This technique also reduces the rate of local infection; 3) This technique reduc es the cost; 4) Few absorption has been found in devitalized bone at the last fo llow up. Immersion within 200 g/L saline then after 95% alcohol provides thoroug h devitalization of tumor hosting bone.

Objective:Research on establishing a better experimental arthritis rat model of cold-dampness arthraligia on rheumatoid arthritis(RA) research.Methods:In order to induce arthritis,the rat's feet were injected with different concentrations of type Ⅱ collagen mixed with Freund's adjuvant;measure the feet swelling degrees of rats,then calculated swelling rate;detect the level of serum sialic acid(SA);observ the synovial histopathology and ultrastructural of rats.Results:The rat joints swell of the group with low concentration of type Ⅱ collagen and completed Freund's adjuvant was rapid and severe,while that of the group with high concentration of type Ⅱ collagen and incompleted Freund's adjuvant was moderate and lasting.The level of serum SA of model groups was higher than the normal group.The histopathology changes of rat's synovium conform to RA.Conclusion:The group injected with high concentration of type Ⅱ collagen and incompleted Freund's adjuvant is the ideal RA model.It is belonged to the symptom of cold-dampness arthralgia,compared with this model,the AA approaches the symptom of heat-dampness arthralgia.